Physico-chemical studies of differences between normal and tumor-producing cells include: 1) The evaluation of morphological differences, by electron microscopy and scanning electron microscopy, between normal hepatocytes and those which are transformed through exposure to chemical carcinogens in vitro. 2) Comparison of kinetic behavior of lactate dehydrogenase from these two cell lines including application of MLAB On-Line Modelling System for the analysis of data collected in the DASAR System (AMINCO, Silver Spring, MD). 3) Demonstration of qualitatively different response of LDH from two hepatocyte lines and LDH-1 purified from red cells when activity is measured with purified NADH vs commercial preparations of NADH. 4) Development of methods to stabilize the enzymes extracted from the hepatocyte lines. 5) Electrophoretic analysis of these LDH preparations using isoelectric focussing techniques and gel electrophoresis. 6) Efforts to purify the LDH for the two hepatocyte lines by column chromatography and HPLC. 7) Human genetic studies: identification of genetic differences in LDH from a patient with a history of spontaneous abortions followed by identification of the chromosome defect.